is atypical depression caused by PEA deficit?

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is atypical depression caused by PEA deficit?

Postby Guest » Wed Jan 23, 2008 7:12 pm

this is a new one to me, but SSRI's do not work for my brand of depression (over sleeping, mood reactivity). the following was posted on an advice board:

K (Feb 6, 2005): D is for Deprenyl. Atypical depressives - read this! Your problem is NOT serotonin! Do not waste months and years of your life on the SSRI merry-go-round.

Your problem is a deficit of phenylethylamine (PEA), the body's "endogenous amphetamine." That is why you want to sleep all the time.

The ideal treatment is to supplement with D-phenylalanine (1-3 grams/day) *AND* low-dose deprenyl (10-15 mg/day). Your depression will disappear in less than 2 weeks.

The primary metabolite of D-phenylalanine is PEA. The deprenyl keeps your brain's monoamine oxidase (MAO-B, which preferentially deanimates PEA) from oxidizing the PEA too quickly. This is why atypical depressives respond to amphetamines and other stimulant drugs, and *NOT* SSRIs.

Keeping the deprenyl at a low dose means you do't have to worry about dietary restrictions. D-PA is preferred because it converts completely to PEA. However it can be hard to find, so subtitute DLPA if you must. L-phenylalanine is useless to you.

Be sure to have your nutritional basics covered as well (B vitamins especially, vitamin C, etc.)

Parnate will probably get the job done, but it is UNselective (it will deanimate MAO-A as well as MAO-B) and thus has dietary restrictions. Deprenyl is selective to MAO-B; it's neuroprotective and may even extend lifespan.

If your doctor will not prescribe a two week trial of low-dose deprenyl, FIND ANOTHER DOCTOR!!! Or order it over the Internet.

Not sure if you're an atypical depressive? Atypicals are not interested in "pursuit activities" such as socializing and shopping. Atypicals ARE interested in "consummator\" (negative-feedback) activities such as sexual orgasm, eating, and sleeping.

This advice worked for me -- hope it does the same for someone else.


Postby Guest » Wed Feb 06, 2008 9:43 pm

Stress precipitates depression and alters its natural history. Major depression and the stress response share similar phenomena, mediators and circuitries. Thus, many of the features of major depression potentially reflect dysregulations of the stress response. The stress response itself consists of alterations in levels of anxiety, a loss of cognitive and affective flexibility, activation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system, and inhibition of vegetative processes that are likely to impede survival during a life-threatening situation (eg sleep, sexual activity, and endocrine programs for growth and reproduction). Because depression is a heterogeneous illness, we studied two diagnostic subtypes, melancholic and atypical depression. In melancholia, the stress response seems hyperactive, and patients are anxious, dread the future, lose responsiveness to the environment, have insomnia, lose their appetite, and a diurnal variation with depression at its worst in the morning. They also have an activated CRH system and may have diminished activities of the growth hormone and reproductive axes. Patients with atypical depression present with a syndrome that seems the antithesis of melancholia. They are lethargic, fatigued, hyperphagic, hypersomnic, reactive to the environment, and show diurnal variation of depression that is at its best in the morning. In contrast to melancholia, we have advanced several lines of evidence of a down-regulated hypothalamic-pituitary adrenal axis and CRH deficiency in atypical depression, and our data show us that these are of central origin. Given the diversity of effects exerted by CRH and cortisol, the differences in melancholic and atypical depression suggest that studies of depression should examine each subtype separately. In the present paper, we shall first review the mediators and circuitries of the stress system to lay the groundwork for placing in context physiologic and structural alterations in depression that may occur as part of stress system dysfunction.


Postby Guest » Wed Feb 06, 2008 9:48 pm

My point, and it comes from a wide variety of sources and is partly opinion, is that your HPA patterns that you are looking at are a result of a loss of circuits that normally innervate those glands and circuits connected to reward and stress response, and besides. These circuits attenuate types of response, and in certain conditions, the result is that you get feedback abnormalities, whilst in others, the stress response is sustainable. That is, the tissue areas that are responsible for hormonal regulation in the HPA axis are neurologically regulated and depending on combinations of signalling respond in various ways to to stimuli. Further, I suggest that when parts of the OFC and PFC are switched 'on' this response cascade is different, and effected all the way down to the activity of various local structures. This posits that a sort of network of 'vagus' type nerves exists throughout the brain and HPA and periphery based on electrical signal strength and synaptically released chemical modulators and modifies the way the system responds to different states of excitation, based upon long-range influences of what other systems are switched on.
Not a loss, a hypertrophy. And yes, when the OFC/PFC do their job, it's exactly like that-- direct electrical suppression of the amygdala.

In this way, your stimulants may work in a different way than you envisage, they may worrk by hitting wider global aspects of the system, whereas I think you are saying that these chemical targets hit particular circuits already involved and change them. So is it the change in the HPA axis that 'releases' the higher functions and healthier cognitive behavior, or is it a peripheral brain action (top down rather than bottom up changes) that antagonises abnormal stress responses or excessive feedback downregulation? Either way, both interesting ways of looking at the problem and maybe it is a bit of both.

It is possible the stimulants also enhance the OFC/PFC abilities to regulate emotion as you say. Of course, this would have to be confirmed in long-term studies, as something that works short-term may or may not be favorable long-term. Cocaine can relieve short-term depression, but in the long run is too intense, euphoric, and abrupt to be of theraputic value.

I think any potential value of amphetamine-like stimulants in normalizing HPA axis functioning is a component of a greater system, certainly. Emotional control must still be learned at a higher level, and the memories within the amygdala must be desensitized; even if you have great emotional control, a persistant battle of the suppression of emotion is very taxing, as has been shown in mPFC hyperactivation in depression. Part of it is dealing with things after they have arisen, but part of it is also lessening their arise.


Postby Guest » Thu Feb 07, 2008 2:46 pm


L-deprenyl (DPR) is a drug developed in the 1960s by Dr. Joseph Knoll. Research has shown DPR to be a safe and multi-faceted drug. At doses of 10-15mg/day or less for humans, DPR is a selective MAO-B inhibitor. MAO-A enzymes break down 5-HT and NA, while MAO-B enzymes break down DA and phenylethylamine (PEA). Classic MAOIs, such as phenelzine and tranylcypromine, inhibit both MAO-A and MAO-B. Classic MAOIs also routinely suffer from the "cheese effect" - the tendency to promote serious, even fatal high blood pressure crises from ingestion of tyramine-rich foods such as aged cheeses and wines. DPR is remarkably free from the "cheese effect" even at typically high daily doses of 30-60mg (4,30). DPR also suppresses the free radical/oxidant stress associated with increased DA neuron activity, as occurs in Parkinson's disease (31). DPR protects DA neurons in monkeys from MPTP, a neurotoxin that has caused rapid-onset Parkinson's disease in humans who unwittingly consumed it in recreational drugs (32). DPR has extended the average life span of male rats beyond the maximum age of death of the species. And DPR has been successfully used as an antidepressant.

In 1980 Mendelwicz and Youdin reported results from a double-blind study comparing placebo, 300mg 5HTP, and 5HTP plus DPR. The 18 patients receiving DPR plus 5HTP experienced depression relief significantly greater than those receiving placebo or 5HTP alone (34).

Quitkin and co-workers found DPR to be superior to placebo in a 6 week trial with 17 atypical depressive patients, and relatively free of side effects. 9/10 positive DPR responders required a 30mg/day DPR dosage. At doses above 20mg, DPR is no longer a selective MAO-B inhibitor, but also begins to suppress MAO-A activity as well, as do standard MAOIs. Nonetheless, Quitkin noted: "There were no reported hypertensive ["cheese effect"] episodes.... L-deprenyl's relative freedom from other MAOI side effects may prove to be of major importance.... Several patients on a regimen of standard MAOIs tolerated a six-week regimen of L-deprenyl quite well." (4)

J. Mann and colleagues reported positive antidepressant effect with DPR in a 44-patient double blind study in 1989. "...after six weeks and at higher doses (averaging about 30mg/d fro the second three weeks), [DPR] was superior to placebo in antidepressant effect with a positive response rate of 50% vs. 13.6% and with a 41% reduction in the Hamilton depression Rating Scale mean score vs. 10% in the placebo-treated group. No hypertensive crises were seen. The rate of occurrence of side effects with [DPR] was no greater than with placebo.... [DPR] is an effective antidepressant in a dose range where it is distinguished by the absence of many of the side effects typical of the nonselective MAO inhibitors." (33)

Based on a double blind, crossover study of placebo vs. 3 weeks of DPR at 60mg/day dosage, T. Sunderland and co-workers reported in 1994 that "Selegiline [DPR] appears to be an effective antidepressant in older patients with treatment-resistant depression.... No serious side effects were noted during our study.... there was... an overall reduction in anxiety, and a decrease in self-reported irritability." (30)

All of the preceding studies were relatively short-term, typically 3 to 6 weeks. Although only minimal side effects were noted, even at the unusually high DPR doses of 30-60 mg/day, the researchers did express concern about possible side effects at these higher doses with more typical long-term (months to years) antidepressant usage. Two successful studies with treatment-resistant depressives have been done, however, that used very modest DPR doses of 5-10mg/day. At this low dose, DPR remains a purely MAO-B inhibitor and is normally fairly side-effect free, even with long-term use.

In 1984 W. Birkmayer and colleagues reported their results from an open study of 155 serious, treatment-resistant depressives. "...102 unipolar [out-] patients... had depression for 3 to 15 years (range); only patients with at least five depressed phases were studied. Usual antidepressant treatment was not successful before the start of a combined L-deprenyl - L-phenylalanine treatment. L-phenylalanine (250mg) and L-deprenyl (5-10mg) were given orally as a single morning dose for 28 to 96 days.... [53 inpatients] had severe unipolar depression for 3 to 15 years; again only patients with at least five episodes of depression were included.... Moreover, usual antidepressants were not effective in this group. L-phenylalanine (250mg) and L-deprenyl (10mg) were given intravenously as morning dose. The duration of this combined treatment was between 14 and 28 days.... After 10 daily infusion we reduced to twice weekly and continued later with oral treatment. In a few patients this [oral] treatment was continued up to 24 months... without any loss of antidepressant effect." (35)

Sleeplessness, tension and anxiety were noted as adverse reactions - these are symptoms of DA/NA over-activation uncompensated for by counterbalancing serotonin activation - Tryp would have been appropriate to complement the DPR/phenylalanine treatment. Birkmayer reports surprisingly excellent results based on modified Hamilton depression rating scale and global clinical impressions: 68.5% full remission and 21.5% moderate effect in the outpatients, with 69.5% full remission and 11% mild and moderate effects in the outpatients.

In 1991 H.C. Sabelli described his results from a small study with 10 treatment-resistant major depressives. Treatment consisted of 5 mg DPR/day, 100 mg vitamin B6/day, and 1 gram phenylalamine a.m. and p.m., with gradual increase to 6 gm/day if needed. "Nine out of 10 patients experienced mood elevation within hours of phenylalamine administration, and 6 viewed their episodes of depression as terminated within 2 to 3 days. Global Assessment Scale scores were significantly lowered after 3 days... and the improved scores were still observed 6 weeks later." (36)

Both the Birkmayer group and Sabelli relate the combined DPR/phenylalamine treatment to enhancement of phenylethylamine (PEA) metabolism. PEA and DA are the main substrates for MÅO-B, which DPR inhibits. PEA is formed from phenylamine with the help of a B6-activated enzyme. PEA is a trace amine that may potentate neuronal firing rates of NA/DA neurons, especially when they're underactive (37). Sabelli has shown that depressives have significantly lower blood and urine levels of PAA (the chief PEA breakdown product) than non-depressed controls. He also notes that effective antidepressant treatment usually increases urinary PAA excretion, while antidepressant treatment that fails to successfully ameliorate depression also fails to increase urinary PAA excretion. Low values of PAA excretion were observed in both retarded and agitated depressives (38). In addition to being converted to PEA, phenylalamine can also be converted into the two "yang" neurotransmitters, NA and DA (39). Thus, a low dose DPR (5-10 mg), moderate dose l-phenylalamine (250 - 500 mg once or twice daily) and 50 -100 mg dose of vitamin B6 regimen may serve to enhance mood, drive, and energy in the "apathetic-inhibited" type of depression, while Tryp may serve to inhibit potential "overactivation" side effects of insomnia, anxiety and irritability.


Postby Guest » Tue Feb 12, 2008 5:54 pm

Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress.
J Psychosom Res 2002 Oct;53(4):865-71
"The stress system coordinates the adaptive responses of the organism to stressors of any kind.(1). The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine (LC/NE)-autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. The CRH and LC/NE systems stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the hypothalamic beta-endorphin system, which suppresses pain sensation and, hence, increases analgesia. CRH inhibits appetite and activates thermogenesis via the catecholaminergic system. Also, reciprocal interactions exist between the amygdala and the hippocampus and the stress system, which stimulates these elements and is regulated by them. CRH plays an important role in inhibiting GnRH secretion during stress, while, via somatostatin, it also inhibits GH, TRH and TSH secretion, suppressing, thus, the reproductive, growth and thyroid functions. Interestingly, all three of these functions receive and depend on positive catecholaminergic input. The end-hormones of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids, on the other hand, have multiple roles. They simultaneously inhibit the CRH, LC/NE and beta-endorphin systems and stimulate the mesocorticolimbic dopaminergic system and the CRH peptidergic central nucleus of the amygdala. In addition, they directly inhibit pituitary gonadotropin, GH and TSH secretion, render the target tissues of sex steroids and growth factors resistant to these substances and suppress the 5' deiodinase, which converts the relatively inactive tetraiodothyronine (T(4)) to triiodothyronine (T(3)), contributing further to the suppression of reproductive, growth and thyroid functions. They also have direct as well as insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome X) and direct effects on the bone, causing "low turnover" osteoporosis. Central CRH, via glucocorticoids and catecholamines, inhibits the inflammatory reaction, while directly secreted by peripheral nerves CRH stimulates local inflammation (immune CRH). CRH antagonists may be useful in human pathologic states, such as melancholic depression and chronic anxiety, associated with chronic hyperactivity of the stress system, along with predictable behavioral, neuroendocrine, metabolic and immune changes, based on the interrelations outlined above. Conversely, potentiators of CRH secretion/action may be useful to treat atypical depression, postpartum depression and the fibromyalgia/chronic fatigue syndromes, all characterized by low HPA axis and LC/NE activity, fatigue, depressive symptomatology, hyperalgesia and increased immune/inflammatory responses to stimuli."


Postby Guest » Wed Apr 30, 2008 6:11 pm



Re: is atypical depression caused by PEA deficit?

Postby DiamondDave » Fri Mar 20, 2009 1:49 am

Firstly, I stumbled across this message board (& website) completely by accident when Googling "Atypical Depression". If the fact that I'm male offends anyone, then I apologise.

The quote from the advice board at the top of this topic has been an obsession of mine for years. I even contacted the owner of the website that the post originally appeared on and asked him to put me in touch with the original author, but he was unable to.

Clearly most of the replies to this topic are from intelligent & knowledgeable people, and as such I'd be extremely grateful if anyone has any thoughts or advice for me once they have read about my own situation. You can find all the grizzly details here:

Particularly relevant are my "Journal Entries" dated April 11, 2008 & March 19, 2009 (today).

Many thanks in advance for any guidance you can offer.


Re: is atypical depression caused by PEA deficit?

Postby quest51 » Wed Feb 13, 2013 2:14 am

This reply is years after this thread started, but I do have a question for 'Guest'. 'Guest' wrote:
Your problem is a deficit of phenylethylamine (PEA), the body's "endogenous amphetamine." That is why you want to sleep all the time.

The ideal treatment is to supplement with D-phenylalanine (1-3 grams/day) *AND* low-dose deprenyl (10-15 mg/day). Your depression will disappear in less than 2 weeks.

The primary metabolite of D-phenylalanine is PEA. The deprenyl keeps your brain's monoamine oxidase (MAO-B, which preferentially deanimates PEA) from oxidizing the PEA too quickly. This is why atypical depressives respond to amphetamines and other stimulant drugs, and *NOT* SSRIs.

Keeping the deprenyl at a low dose means you do't have to worry about dietary restrictions. D-PA is preferred because it converts completely to PEA. However it can be hard to find, so subtitute DLPA if you must. L-phenylalanine is useless to you.

Now, my question is this, instead of using deprenyl, I am thinking of using Rhodiola Rosea which is an herb supplement shown to be a mild MAO-B and MAO-A inhibitor, and people have had a lot of success using it for treating their atypical depression. Would Rhodiola + d-phenylalanine achieve similar results as deprenyl+d-pa?

Also, as Rhodiola apparently inhibits MAO-A, would dietary restrictions be necessary or is the affect not strong enough (compared with deprenyl at high doses) to cause worry about tyramine.

Lastly, the studies I've read regarding deprenyl (selegiline) as beneficial for atypical depression all showed improvement when dosage was high, 40-60mg+/day, and that low doses of depranyl did not show benefit. You suggest low dose (10-15mg), will it be beneficial?

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